Abstract
Titanium dioxide (TiO(2)), a white color food additive, is widely used in bakery products, candies, chewing gums, soups, and creamers. Concerns about its potential genotoxicity have recently emerged, particularly following the European Union's ban on its usage as a food additive due to its genotoxicity potential. Conflicting in vitro and in vivo results regarding its genotoxicity highlight the need for further in-depth investigation. Moreover, food additives can interact with food components or biological matrices, potentially altering their biological responses and genotoxicity. In this study, we evaluated the interactions between two different sizes of additive TiO(2) particles and food or biological matrices, including albumin, fetal bovine serum (FBS), and glucose. The results showed that the hydrodynamic diameters of TiO(2) increased upon interaction with albumin or FBS, but not with glucose. The presence of albumin or FBS reduced TiO(2)-induced cytotoxicity, oxidative stress, in vitro intestinal transport, and ex vivo intestinal absorption to untreated control levels, regardless of particle size. While TiO(2) caused DNA damage in intestinal Caco-2 cells, the interactions with albumin or FBS significantly reduced the DNA damage to levels comparable to untreated controls. The DNA damage was closely related to oxidative stress caused by TiO(2). These findings suggest that the interaction of TiO(2) with albumin or FBS, resulting in increased hydrodynamic diameters, mitigates its cytotoxicity, oxidative stress, intestinal transport, and genotoxicity. Further investigation is required to fully understand the potential genotoxicity of TiO(2) in food contexts.